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Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.
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Infecções por Citomegalovirus , Transplante de Coração , Humanos , Hematopoiese Clonal/genética , Rejeição de Enxerto/epidemiologia , Coração , HematopoeseRESUMO
AIMS: The heterogeneous phenotype of hypertrophic cardiomyopathy (HCM) is still not fully understood. Clonal haematopoiesis (CH) is emerging as a cardiovascular risk factor potentially associated with adverse clinical events. The prevalence, phenotype and outcomes related to CH in HCM patients were evaluated. METHODS AND RESULTS: Patients with HCM and available biospecimens from the Peter Munk Cardiac Centre Cardiovascular Biobank were subjected to targeted sequencing for 35 myeloid genes associated with CH. CH prevalence, clinical characteristics, morphological phenotypes assessed by echocardiogram and cardiac magnetic resonance and outcomes were assessed. All patients were evaluated for a 71-plex cytokines/chemokines, troponin I and B-type natriuretic peptide analysis. Major adverse cardiovascular events (MACE) were defined as appropriate implantable cardioverter-defibrillator shock, stroke, cardiac arrest, orthotopic heart transplant and death. Among the 799 patients, CH was found in 183 (22.9%) HCM patients with sarcomeric germline mutations. HCM patients with CH were more symptomatic and with a higher burden of fibrosis than those without CH. CH was associated with MACE in those HCM patients with sarcomeric germline mutations (adjusted hazard ratio [HR] 6.89, 95% confidence interval [CI] 1.78-26.6; p = 0.005), with the highest risk among those that had DNMT3A, TET2 and ASXL1 mutations (adjusted HR 5.76, 95% CI 1.51-21.94; p = 0.010). Several cytokines (IL-1ra, IL-6, IL-17F, TGFα, CCL21, CCL1, CCL8, and CCL17), and troponin I were upregulated in gene-positive HCM patients with CH. CONCLUSIONS: These results indicate that CH in patients with HCM is associated with worse clinical outcomes. In the absence of CH, gene-positive patients with HCM have lower rates of MACE.
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BACKGROUND: Cardiogenic shock (CS) is associated with high in-hospital mortality. Objective assessment of its severity and prognosis is paramount for timely therapeutic interventions. This study aimed to evaluate the efficacy of the shock index (SI) and its variants as prognostic indicators for in-hospital mortality. METHODS: A retrospective study involving 1282 CS patients were evaluated. Baseline patient characteristics, clinical trajectory, hospital outcomes, and shock indices were collected and analysed. Receiver operating characteristic (ROC) curves were employed to determine the predictive accuracy of shock indices in predicting in-hospital mortality. RESULTS: Of those evaluated, 866 (67.6%) survived until discharge. Non-survivors were older (66.0 ± 13.7 vs. 57.4 ± 16.2, P < 0.001), had a higher incidence of cardiac risk factors, and were more likely to present with acute coronary syndrome (33.4% vs. 16.1%, P < 0.001) and out-of-hospital cardiac arrest (11.3% vs. 5.3%, P < 0.001). All mean shock indices were significantly higher in non-survivors compared with survivors. ROC curves demonstrated that adjusted shock index (ASI), age-modified shock index (AMSI), and shock index-C (SIC) had the highest predictive accuracy for in-hospital mortality, with AUC values of 0.654, 0.667, and 0.659, respectively. Subgroup analysis revealed that SIC had good predictive ability in patients with STEMI (AUC: 0.714) and ACS (AUC: 0.696) while AMSI and ASI were notably predictive in the OHCA group (AUC: 0.707 and 0.701, respectively). CONCLUSIONS: Shock index and its variants, especially ASI, AMSI, and SIC, may be helpful in predicting in-hospital mortality in CS patients. Their application could guide clinicians in upfront risk stratification. SIC, ASI, and AMSI show potential in predicting in-hospital mortality in specific CS subsets (STEMI and OHCA). This is the first study to evaluate SI and its variants in CS patients.
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OBJECTIVES: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients. METHODS: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed. RESULTS: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL. CONCLUSION: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM.
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BACKGROUND: The optimal management of hypertrophic cardiomyopathy (HCM) patients with postoperative atrial fibrillation (POAF) after surgical myectomy remains unknown. We sought to investigate the association between POAF and atrial fibrillation (AF) or cardioembolic events during follow-up to bridge this gap. METHODS: Patients undergoing surgical myectomy at 2 HCM referral centres in North America from 2002 to 2020 were included in this study. Patients with preoperative AF were excluded. POAF was defined as any episode of AF within 30 days after surgery. RESULTS: Of 1176 patients, 375 (31.9%) had POAF. Age (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P < 0.001), premyectomy left atrial diameter (LAD; adjusted HR 1.6, 95% CI 1.32-2.02; P < 0.001), and smoking (adjusted HR 1.60, 95% CI 1.17-2.20; P = 0.001) were associated with POAF on multivariable analysis. Of 934 patients with follow-up data, of duration 4.3 ± 4.1 years, AF was detected in 86 (9.2%). Only POAF (HR 4.20, 95% CI 2.44-7.23; P < 0.001), previous history of stroke (HR 4.81, 95% CI 1.63-14.17; P = 0.01), and postmyectomy LAD (HR 1.80, 95% CI 1.21-2.70; P = 0.004) were associated with AF incidence during follow-up. Cardioembolic events occurred in only 15 patients (1.6%). POAF was not associated with increased cardioembolic risk, with only 3 patients with POAF suffering such an event, all more than 4 years after surgery. CONCLUSIONS: POAF is common in HCM patients undergoing myectomy and is a predictor of AF during follow-up. Over long-term follow-up, cardioembolic events are uncommon. These findings suggest that routine long-term anticoagulation for all HCM patients with postmyectomy AF is not justified after the initial postoperative period.
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Fibrilação Atrial , Cardiomiopatia Hipertrófica , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Relevância Clínica , Fatores de Risco , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/cirurgia , Período Pós-Operatório , Complicações Pós-Operatórias/epidemiologiaRESUMO
Background: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU. Methods: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied. Patient demographics, admission diagnosis, critical care resources, complications, in-hospital mortality, and CICU and hospital length of stay were recorded. Results: A total of 8865 consecutive admissions occurred, with a median age of 64.9 years. The most common primary cardiac diagnoses were acute decompensated heart failure (17.8%), non ST-elevation myocardial infarction (16.8%), ST-elevation myocardial infarction (15.5%), and arrhythmias (14.7%). Cardiogenic shock was seen in 13.2%, and out-of-hospital cardiac arrest in 4.1%. A noncardiovascular admission diagnosis accounted for 13.9% of the cases. Over the period studied, rates of admission were higher for cardiogenic shock (P < 0.001 for trend), with a higher use of critical care resources. Additionally, rates of admission were higher in female patients and those who had chronic kidney disease and diabetes. The in-hospital mortality rate of all CICU admissions was 13.2%, and it was highest in those with noncardiac conditions, compared to the rate in those with cardiac diagnoses (29.4% vs 10.6%, P < 0.001). Conclusions: Given the trends of higher acuity of patients with cardiac critical illness, with higher use of critical care resources, education streams for critical care within cardiology, and alternative pathways of care for patients who have lower-acuity cardiac disease remain imperative to manage this evolving population.
Introduction: L'unité de soins intensifs de cardiologie (USIC) d'aujourd'hui a évolué vers des soins aux patients atteints d'une maladie cardiaque aiguë en phase critique. Nous décrivons la population actuelle de patients cardiaques d'une USIC quaternaires. Méthodes: Les patients consécutifs d'USIC admis à l'USIC de l'Hôpital général de Toronto de 2014 à 2020 ont fait l'objet de l'étude. Les données démographiques des patients, le diagnostic à l'admission, les ressources en soins aux patients en phase critique, les complications, la mortalité intrahospitalière, et la durée de séjour à l'hôpital et à l'USIC ont été enregistrés. Résultats: Il y a eu un total de 8 865 admissions consécutives dont les patients avaient un âge médian de 64,9 ans. Les diagnostics principaux les plus fréquents de maladies cardiaques étaient l'insuffisance cardiaque aiguë décompensée (17,8 %), l'infarctus du myocarde sans élévation du segment ST (16,8 %), l'infarctus du myocarde avec élévation du segment ST (15,5 %) et les arythmies (14,7 %). Le choc cardiogénique a été observé chez 13,2 %, et l'arrêt cardiaque hors de l'hôpital, chez 4,1 %. Un diagnostic d'admission de maladie non cardiovasculaire représente 13,9 % des cas. Durant la période étudiée, les taux d'admission en raison d'un choc cardiogénique étaient plus élevés (P < 0,001 pour la tendance), et entraînaient une utilisation plus élevée de ressources en soins aux patients en phase critique. De plus, les taux d'admission étaient plus élevés chez les patientes, et chez ceux qui avaient une insuffisance rénale chronique et un diabète. Le taux de mortalité intrahospitalière de toutes les admissions à l'USIC était de 13,2 %, et il constituait le taux le plus élevé chez ceux qui avaient des maladies non cardiaques comparativement au taux chez ceux qui avaient des diagnostics de maladies cardiaques (29,4 % vs 10,6 %, P < 0,001). Conclusions: Compte tenu des tendances d'accroissement de la gravité de l'état des patients atteints d'une maladie cardiaque en phase critique et de la plus grande utilisation des ressources en soins aux patients en phase critique, des volets de formation en soins aux patients en phase critique en cardiologie et d'autres protocoles de soins des patients qui ont une maladie cardiaque de plus faible gravité demeurent essentiels à la prise en charge de cette population grandissante.
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AIMS: Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre. METHODS AND RESULTS: We compared the frequency of CH mutations among 341 CS patients and 345 ambulatory heart failure (HF) patients matched for age, sex, ejection fraction, and HF aetiology. The association of CH with survival and levels of circulating inflammatory cytokines was analysed. We detected 266 CH mutations in 149 of 686 (22%) patients. CS patients had a higher prevalence of CH-related mutations than HF patients (odds ratio 1.5; 95% confidence interval [CI] 1.0-2.1, p = 0.02) and was associated with decreased survival (30 days: hazard ratio [HR] 2.7; 95% CI 1.3-5.7, p = 0.006; 90 days: HR 2.2; 95% CI 1.3-3.9, p = 0.003; and 3 years: HR 1.7; 95% CI 1.1-2.8, p = 0.01). TET2 or ASXL1 mutations were associated with lower survival in CS patients at all time-points (p ≤ 0.03). CS patients with TET2 mutations had higher circulating levels of SCD40L, interferon-γ, interleukin-4, and tumour necrosis factor-α (p ≤ 0.04), while those with ASXL1 mutations had decreased levels of CCL7 (p = 0.03). CONCLUSIONS: Cardiogenic shock patients have high frequency of CH, notably mutations in TET2 and ASXL1. This was associated with reduced survival and dysregulation of circulating inflammatory cytokines in those CS patients with CH.
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Insuficiência Cardíaca , Choque Cardiogênico , Hematopoiese Clonal , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Inflamação , Interferon gama , Interleucina-4 , Choque Cardiogênico/etiologia , Fator de Necrose Tumoral alfaRESUMO
Indications of cardiac resynchronization therapy (CRT) do not include exercise-induced left bundle branch block, but functional impairment could be improved with CRT in such cases. A 57-year-old woman with idiopathic dilated cardiomyopathy (ejection fraction 23%) presented with New York Heart Association Class IV and recurrent hospitalizations. During heart transplant evaluation, a new onset of intermittent left bundle branch block was observed on the cardiopulmonary exercise test. CRT was implanted, and 97% resynchronization rate was achieved. In 12 month follow-up, both clinical and prognostic exercise parameters improved. In patients with heart failure with reduced ejection fraction and no left bundle branch block at rest, exercise test can uncover electromechanical dyssynchrony that may benefit from CRT.
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Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/terapia , Frequência Cardíaca/fisiologia , Função Ventricular Esquerda/fisiologia , Bloqueio de Ramo/etiologia , Bloqueio de Ramo/fisiopatologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Early risk stratification is essential for in-hospital management of ST-segment-elevation myocardial infarction. Acute heart failure confers a worse prognosis, and although lung ultrasound (LUS) is recommended as a first-line test to assess pulmonary congestion, it has never been tested in this setting. Our aim was to evaluate the prognostic ability of admission LUS in patients with ST-segment-elevation myocardial infarction. METHODS: LUS protocol consisted of 8 scanning zones and was performed before primary percutaneous coronary intervention by an operator blinded to Killip classification. A LUS combined with Killip (LUCK) classification was developed. Receiver operating characteristic and net reclassification improvement analyses were performed to compare LUCK and Killip classifications. RESULTS: We prospectively investigated 215 patients admitted with ST-segment-elevation myocardial infarction between April 2018 and June 2019. Absence of pulmonary congestion detected by LUS implied a negative predictive value for in-hospital mortality of 98.1% (93.1-99.5%). The area under the receiver operating characteristic curve of the LUCK classification for in-hospital mortality was 0.89 (P=0.001), and of the Killip classification was 0.86 (P<0.001; P=0.05 for the difference between curves). LUCK classification improved Killip ability to predict in-hospital mortality with a net reclassification improvement of 0.18. CONCLUSIONS: In a cohort of patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, admission LUS added to Killip classification was more sensitive than physical examination to identify patients at risk for in-hospital mortality. LUCK classification had a greater area under the receiver operating characteristic curve and reclassified Killip classification in 18% of cases. Moreover, absence of pulmonary congestion on LUS provided an excellent negative predictive value for in-hospital mortality.
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Insuficiência Cardíaca/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Admissão do Paciente , Testes Imediatos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Ultrassonografia , Doença Aguda , Idoso , Feminino , Nível de Saúde , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do TratamentoRESUMO
Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.